DESCRIPTION: (Applicant's Description) The long term goal of this project is to assess the use of photodynamic therapy as a treatment for Barrett's esophagus. Barrett's esophagus is a pre-malignant condition that is being diagnosed in up to 18 percent of patients undergoing endoscopy. It is felt to be responsible for distal esophageal and proximal gastric cancers which are currently the most rapidly increasing tumor in the United States among men. With greater recognition and screening of this condition, the significance and management of superficial neoplastic lesions has become a frequent clinical dilemma. Photodynamic therapy (PDT) would be an ideal alternative therapy to traditional surgical resection since the esophagus can easily be accessed by commonly available endoscopes and treatment can be delivered with simple optical fiber technology with preservation of gut function as opposed to a costly, debilitating, and difficult operation. The effect of photodynamic therapy can be targeted to the mucosa where the neoplastic Barrett's epithelium is initially confined. We have shown that photodynamic therapy can cause regression of large segments of Barrett's esophagus with regeneration of normal squamous mucosa. Unique methods will be use to deliver this therapy. Drug dosimetry will be controlled using a novel fluorescence probe to determine tissue levels of the photosensitizer. Light dosimetry will be improved by utilizing a balloon centering device to flatten the esophageal mucosa. The most important issue regarding PDT will be to assess whether treatment can alter the biological behavior of Barrett's epithelium. The development of PDT as a therapy for Barrett's esophagus could prevent the development of distal esophageal and proximal gastric cancers and provide unique information regarding the relationship of dysplasia to biological behavior of the cells.